Neoadjuvant Cemiplimab for Non-Small Cell Lung Cancer

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Metastatic disease, Active autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, cemiplimab (an immunotherapy), both alone and with another drug, fianlimab, to evaluate their effectiveness in treating non-small cell lung cancer (NSCLC). The goal is to determine if these drugs can shrink tumors before surgery and to understand any side effects. Individuals with NSCLC who are candidates for surgery and have not recently undergone cancer treatments may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that cemiplimab is generally safe for people. Studies indicate it has a strong safety record when treating advanced non-small cell lung cancer (NSCLC). In a large group of patients, only a small percentage experienced lung inflammation, known as pneumonitis. Specifically, out of 1,281 patients, about 2.6% had this side effect, and for most, it was mild to moderate. Only 0.3% experienced severe cases.

For fianlimab, less information is available. However, the early phase of the study suggests that fianlimab has shown enough promise in terms of safety to continue testing. Clinical trials are designed to closely monitor safety, and participants remain under careful observation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cemiplimab because it offers a new way to tackle non-small cell lung cancer (NSCLC). Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, cemiplimab is an immunotherapy that specifically works by blocking the PD-1 pathway. This action helps the immune system recognize and fight cancer cells more effectively. Additionally, cemiplimab is used both before and after surgery, potentially reducing tumor size initially and preventing recurrence. This targeted approach could lead to improved outcomes for patients compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that cemiplimab holds promise for treating non-small cell lung cancer (NSCLC). In this trial, some participants will receive cemiplimab with platinum-based chemotherapy, which studies have found can double the five-year survival rate for NSCLC patients. Cemiplimab is already approved as a first-choice treatment for NSCLC when combined with platinum-based chemotherapy. It targets PD-1, a part of immune cells, helping the body fight cancer more effectively. Another arm of this trial will examine the combination of cemiplimab and fianlimab, which targets LAG-3, a protein that might help cancer evade the immune system. Using cemiplimab and fianlimab together could offer a new way to enhance the immune system's ability to combat cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with resectable Non-Small Cell Lung Cancer (NSCLC), Liver Cancer (HCC), or Head and Neck Squamous Cell Carcinoma (HNSCC) who are in good health, have no major surgeries recently, aren't on immunosuppressants, and haven't had recent cancer treatments. NSCLC patients must be non-smokers without certain gene mutations.

Inclusion Criteria

I am willing to undergo a biopsy before starting cemiplimab treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

I am considered fit for surgery to remove my tumor.

Exclusion Criteria

I have never smoked or have smoked less than 100 cigarettes in my lifetime.

I haven't had encephalitis, meningitis, or uncontrolled seizures in the last year.

I haven't had cancer treatment or radiation in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive cemiplimab, and in some cohorts, fianlimab or platinum doublet, prior to surgery

Up to 28 days

Surgery

Participants undergo surgery to assess major pathologic response and other primary endpoints

Adjuvant Treatment

Participants receive cemiplimab, and in some cohorts, platinum doublet or standard of care radiation/chemotherapy, post surgery

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after treatment

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab

Trial Overview The trial is testing cemiplimab alone and combined with fianlimab before surgery to see if they shrink tumors safely. Both drugs are monoclonal antibodies; cemiplimab targets PD-1 receptors while fianlimab blocks LAG-3 proteins involved in cancer.

How Is the Trial Designed?

Group I: Cohort C Experimental Treatment 1 Intervention

Cemiplimab prior to surgery; standard of care radiation and/or chemotherapy followed by cemiplimab post surgery (HNSCC) Not open for accrual

Group II: Cohort B3 Experimental Treatment 2 Interventions

Cemiplimab and fianlimab before and after surgery (HCC)

Group III: Cohort B2 Experimental Treatment 1 Intervention

SBRT 8 Gy X 3 fractions followed by cemiplimab prior to surgery; cemiplimab post surgery (HCC)

Group IV: Cohort B Experimental Treatment 1 Intervention

Cemiplimab prior to surgery; cemiplimab post surgery (HCC)

Group V: Cohort A3 Experimental Treatment 2 Interventions

Platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual

Group VI: Cohort A2 Experimental Treatment 2 Interventions

Cemiplimab and platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual

Group VII: Cohort A1 Experimental Treatment 2 Interventions

Cemiplimab prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., et al.[2023]

Cemiplimab significantly improves overall survival in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 levels, adding 0.546 quality-adjusted life years (QALYs) compared to chemotherapy.

The treatment is considered cost-effective, with an incremental cost-effectiveness ratio of $40,390 per QALY gained, and a 100% probability of being cost-effective at a willingness-to-pay threshold of $150,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Cemiplimab Versus Chemotherapy as First-Line Treatment in Advanced NSCLC with PD-L1 Expression Levels of at Least 50. Wang, L., Peng, Y., Zeng, X., et al.[2021]

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

At 35 months of follow-up, patients with advanced non-small-cell lung cancer and high PD-L1 expression treated with cemiplimab had a median overall survival of 26.1 months, significantly better than the 13.3 months for those receiving chemotherapy, indicating a strong survival benefit from cemiplimab.

The addition of chemotherapy to cemiplimab after disease progression resulted in a median overall survival of 15.1 months, suggesting that this combination could be an effective second-line treatment option for patients with advanced non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Özgüroğlu, M., Kilickap, S., Sezer, A., et al.[2023]

In patients with advanced non-small-cell lung cancer (NSCLC) and high PD-L1 expression (≥50%), cemiplimab showed significant improvements in progression-free survival (PFS) and objective response rate (ORR) compared to pembrolizumab, based on a systematic review and network meta-analysis of randomized-controlled trials.

Cemiplimab demonstrated comparable overall survival (OS) and similar safety profiles to pembrolizumab, indicating it is a viable first-line treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50. Freemantle, N., Xu, Y., Wilson, FR., et al.[2022]

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

Neoadjuvant immunotherapy, particularly the combination of nivolumab and chemotherapy, has shown promising results in treating non-small cell lung cancer, leading to significant pathological responses and clinical benefits in selected patients.

Nivolumab with chemotherapy is the first FDA-approved immunotherapy for non-small cell lung cancer in the neoadjuvant setting, but further studies are needed to assess long-term efficacy and potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Progress of Neoadjuvant Immunotherapy for Non-small Cell Lung Cancer]. Guo, C., Zhang, J., Li, S.[2022]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

Citations

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Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... Late-breaking data from exploratory analyses at WCLC show Libtayo plus chemotherapy demonstrates a more than double five-year overall ...

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Study Details | NCT06918132 | Cemiplimab and Fianlimab ... This phase II trial tests how well a fixed dose combination (FDC) of cemiplimab and fianlimab before surgery (neoadjuvant) works in treating patients with ...

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Spotlight on Cemiplimab-rwlc in the Treatment of Non- ... Cemiplimab-rwlc, which is a highly potent, hinged, stabilized, human IgG 4 monoclonal antibody directed against PD-1, is a newly FDA-approved immunotherapy ...

4. targetedonc.com targetedonc.com/view/cemiplimab-5-year-data-show-improved-survival-in-high-pd-l1-nsclc

Cemiplimab 5-Year Data Show Improved Survival in High ... Cemiplimab 5-Year Data Show Improved Survival in High PD-L1 NSCLC ... During a live event, Bruna Pellini, MD, discussed the efficacy of cemiplimab ...

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LIBTAYO® (cemiplimab-rwlc) in Advanced NSCLC LIBTAYO in combination with platinum-based chemotherapy is indicated for the first-line treatment of adult patients with non–small cell lung cancer (NSCLC) ...

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Safety, efficacy, and quality of life with cemiplimab ... Background: Immune checkpoint inhibitors have shown promise in treating advanced non-small cell lung cancer and have a solid safety profile.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424016101

P4.11E.23 Real-World Data (RWD) Of First-Line ... The aim of this study was to assess the real-world outcomes of NSCLC patients receiving cemiplimab as first-line therapy.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20572

Evaluating the safety and effectiveness of cemiplimab in ... This observational study (NCT06269133) will assess the RW safety and effectiveness of first-line (1L) treatment of aNSCLC with cemiplimab in combination with ...